Cardiotoxicity of Cancer Therapy (CCT)

Официальное название

Cardiotoxicity of Cancer Therapy: Mechanisms and Predictors

Обзор

The objective of this study is to define the clinical significance of mechanistic biomarkers (including Neuregulin-1Beta) and novel echocardiographic measures of cardiac function in predicting the incident risk of cancer therapy cardiotoxicity.

Подробное описание

The overall study objectives are:

1. To determine the longitudinal relationships between circulating markers, such as Neuregulin (NRG)-1Beta levels and incident risk of adverse cardiovascular outcomes in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that a sustained increase in NRG-1Beta, indicative of enhanced cardiac stress with exposure to chemotherapeutic agents, is predictive of an increased risk of cardiac dysfunction and heart failure. 2. To study the single nucleotide polymorphism (SNP)/haplotype variation in pathways of interest, such as the Neuregulin/Epidermal Growth Factor (ErbB) signaling pathway, on incident risk of adverse cardiovascular outcomes. We hypothesize that there will be SNP/haplotypes variations that are associated with incident cardiovascular outcomes. 3. To determine the longitudinal relationships between novel echocardiographic measures, such as strain and strain rate and incident cardiac dysfunction in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that early declines in strain and strain rate are predictive of an increased risk of future cardiac dysfunction and heart failure. 4. To explore the changes in biomarkers such as NRG-1Beta levels and the relationships with novel echocardiographic measures of cardiac function. 5. To create a biobank as a future resource for additional questions in novel biomarkers and genetics. 6. To determine the long-term effects of cancer therapy cardiotoxicity by following patients yearly for 5 years after their exposure to cancer therapy, with the option to extend up to an additional 5 years.

Вмешательства

• Диагностический тест Echocardiography
  Prior to chemotherapy, prior to and after anthracyclines, every 6 weeks during trastuzumab, and yearly for up to 10 years.
• Другое Blood Collection
  Drawn at first chemo treatment and periodically during treatment (exact schedule varies with clinically ordered treatment plan), then annually for up to 10 years. Blood is banked for future biomarker testing.
• Другое Symptoms Questionnaire
  Survey collected at first chemotherapy, periodically during therapy (exact schedule determined by clinically ordered treatment regimen), and annually for up to 10 years.

Первичные конечные точки

• Cardiac dysfunction or signs or symptoms of heart failure [Срок оценки: 15 years]

Вторичные конечные точки (1)

• Change in quantitated Left Ventricular Ejection Fraction (LVEF) [Срок оценки: 15 years]

Критерии участия

Критерии включения

• Age 18 years or older
• HER-2 positive breast cancer designated to receive trastuzumab chemotherapy with or without prior exposure to anthracycline-based chemotherapy
• Non-HER-2 positive breast cancer designated to receive treatment with an anthracycline-containing regimen

Критерии исключения

• Other contraindications to trastuzumab or anthracycline chemotherapy.
• Vulnerable populations

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Abramson Cancer Center of the University of Pennsylvania — Philadelphia

Публикации

• Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DeMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Tang WHW, Liu P, Ky B. Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction. J Am Heart Assoc. 2020 Jan 21;9(2):e014708. doi: 10.1161/JAHA.119.014708. PMID 31959034
• Upshaw JN, Finkelman B, Hubbard RA, Smith AM, Narayan HK, Arndt L, Domchek S, DeMichele A, Fox K, Shah P, Clark A, Bradbury A, Matro J, Adusumalli S, Carver JR, Ky B. Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy. JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 2):198-210. doi: 10.1016/j.jcmg.2019.07.018. Epub 2019 Sep 18. PMID 31542526
• Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nunez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F PMID 30987448

Идентификаторы

NCT: NCT01173341 · UPCC 09110

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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